Background: Oxytocin (OT), a cardiac hormone, is reported as the cardiomyogenic factor for embryonic stem cells. It also stimulates the differentiation of cardiac progenitor cells to cardiomyocytes. We found that oxytocin receptor (OTR) was highly expressed in UCB-MSCs in compared with bone marrow (BM)-MSCs, and designed this study to elucidate whether OT play important roles in UCB-MSCs cellular events. Methods: MSC were isolated and cultured from UCB and BM. MSCs were treated with OT (100 nM). Angiogeneic potential was evaluated by tube formation, and cell migration was assessed by wound healing assay. The transwell migration activity was determined by using modified Boyden chamber assay. The expressions of OTR, vWF, angiopoietin (Ang)-1, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analysis. To assay the enzymatic activities of MMP-2 and MMP-9, MSCs cultured media were analyzed by zymography. Results: The expression level of OTR was higher in UCB-MSCs than BM-MSCs. The proliferation rate of UCB-MSCs was not changed during treatment with OT (0, 10, 100, 1000 nM). Tube formation was attenuated by OT, and cell migration rate was not changed by OT treatment. On the other hand, transmigration activity was drastically accelerated by OT treatment. To examine whether MMP expression was induced by OT, mRNA level of MMP-2 and MMP-9 was determined by RT-PCR. OT increased the MMP-2 mRNA in proportion to OT concentration (10, 100, 1000 nM) in 1 hr. MMP-9 mRNA, not expressed in UCB-MSCs, was increased by 100 nM and 1000 nM OT treatment in 1 hr and prolonged to 24 hr. To examine whether MMP-2 and MMP-9 activity was increased by OT, the UCB-MSCs were cultured for 24 hr in the presence or absence of OT (100 nM), and cultured media was analyzed by zymograph. Both MMP-2 and MMP-9 activities were increased by OT treatment. Conclusions: OT accelerated the transmigration activity of UCB-MSCs, and OT could be utilized to improve the efficient targeting of UCM-MSCs to injured heart tissue.